January Editorial - Taking a Reasoned Approach to Drug Warnings

Posted on
12/22/04

by Michele Kaufman, PharmD

Lately, not a day goes by without reading about a new drug warning, even in the lay press. Or, should I say, particularly in the lay press. As noted on the FDA web site, through numerous online newsletters, in other professional literature, and in the other media, drug warnings continue to evolve. This is due to the many limitations of study design, including duration of pre-marketing clinical trials. Additionally, since pre-marketing clinical study inclusion criteria are very strict, patients are practically hand-picked based on medical history and (often times, lack of) any current medications. Included patients are not very numerous, are usually relatively healthy, on no medications with limited chronic disease states (or no concomitant disease states), and are treated for relatively short periods of time. The main limitation of a short study is that problems associated with long-term use are never realized. Rare reactions are not ?identified? in pre-marketing studies because too few patients are studied. Therefore it is sometimes thought that you should prescribe newly FDA-approved drugs with caution.

Post-marketing surveillance is mandated because of these reasons and spontaneous adverse event reporting is recommended through the FDA MedWatch program for healthcare professionals. Pharmaceutical manufacturers are mandated to report serious and new adverse events for recently FDA-approved drugs (approved within the last 2 years).

New safety alerts and labeling can be found at http://www.fda.gov/medwatch. The MedWatch site has a free e-list that will deliver safety alert summaries directly into your e-mail in-bin, so it is worth checking out to keep on top of the subject.

According to a relatively recent article in the Wall Street Journal (9/15/04, page D4) up until that date, the FDA had issued 45 safety alerts on drugs, medical devices and dietary supplements so far. Since then, an additional 18 safety alerts have been issued for a total of 63 through December 22, 2004. In 2003, the FDA issued 53 safety alerts, compared with just 25 alerts in 1996.

Many healthcare providers wonder how to best handle safety alerts. Do you keep the patient on the medication if he or she is doing well, or do you discontinue treatment? Each case becomes a risk versus benefit analysis, and don?t be fooled by pharmaceutical advertising. After researching and reading all the available information about the alert (not just information provided by the drug?s manufacturer or from pharmaceutical representatives), review the patient?s medical history and medication history, and then determine if the drug in question is needed. Is there an alternative with long-term safety data? Is there a similar generic that can be used? Can you still use the drug but at a lower dose (the same dose)? What about using a different brand medication with a longer history than the drug in question? Remember that just because there is a warning of a reaction or an interaction, you may be able to treat through it, or recommend to the prescriber with the available information to treat through it.

If you don?t have access to good references, ask your drug information pharmacist, a drug information center, or your clinical pharmacist. You can also contact the FDA CDER Drug Information Center at 1-301-827-4570 during business hours. The main number at the FDA is 1-888-463-6332. Once all the information is compiled and everything is logically thought out, a clear decision about how to proceed can be made. Of course if your favorite drugs get removed from the market (like Vioxx or Rezulin), you definitely need to seek out alternate routes.

On a similar note, a recent survey noted that two-thirds of FDA scientists said that they lacked confidence in the FDA\'s ability to adequately monitor the safety of drugs on the market. According to survey data, only 12 percent of FDA scientists were completely confident that FDA \"labeling decisions adequately address key safety concerns.\" Greater than 36 percent of FDA scientists were either not at all confident or only somewhat confident that the FDA\'s \"final decisions adequately assess the safety of a drug.\"

Furthermore, nearly one in five scientists reported in the survey that they \"have been pressured to approve or recommend approval\" for a drug \"despite reservations about the safety, efficacy or quality of the drug.\"